Authors
Fabiano Bichuette Custodio1 Emerson Quintino de Lima2
1 Medical School of São José do Rio Preto (FAMERP). University Hospital of the Federal University of Triangulo Mineiro (UFTM) - Uberaba - MG. 2 Medical School of São José do Rio Preto (FAMERP).
Submitted on: 01/31/2012. Approved on: 03/18/2013.
Correspondence to:
Emerson Quintino de Lima. Nephrology Program - Base Hos-pital - Medical School of São José do Rio Preto (FAMERP). Av. Brigadeiro Faria Lima, nº 5544, Vila São Pedro, São José do Rio Preto, SP, Brazil. CEP:15090-000. E-mail: equintino@uol.com.br Tel: (17) 3201-5000. Ramal 5169.
Extended hemodialysis in acute kidney injury
About 10% of patients in the intensive
care unit which develop acute renal
fail-ure will depend on renal replacement
therapy. Although there are no data
showing reduction in mortality when
compared with intermittent therapy,
continuous therapies provide higher
cu-mulative doses of dialysis and greater
hemodynamic stability. However, have
high costs and are not available in many
centers. In this context the Extended
Hemodialysis gaining ground in clinical
practice because it combines the
hemo-dynamic tolerability, slow and sustained
solute control and effective doses of
continuous dialysis therapies associated
with reduced costs and logistics
facili-ties of intermittent therapy.
A
BSTRACTKeywords:
acute kidney injury; dialysis;
Intensive Care Units.
I
NTRODUCTIONAcute Kidney Injury (AKI) is a common
complication in critically ill patients,
affec-ting up to 30% of those admitted to the
Intensive Care Unit (ICU). Unfortunately,
despite major advances in the treatment
of these patients, AKI mortality remains
high.
1About 5%-10% of ICU patients develop
acute kidney failure requiring renal
re-placement treatment (RRT), while in more
severe forms of AKI, RRT-dependence
exceeds 60%.
2RRT modes in this
popu-lation may be intermittent (conventional
hemodialysis and peritoneal dialysis) or
continuous (continuous hemodialysis,
he-mofiltration or hemodiafiltration).
3The
choice of the optimal method depends on
the patient’s clinical status, the medical
knowledge and the availability in each
cen-ter.
4Although there are studies comparing
these treatment modalities, differences on
mortality and renal function recovery
have not been investigated.
5-8The main
limiting factor of intermittent treatment
in critically ill patients is hemodynamic
instability. Intradialytic hypotension is
associated with dialysis-related factors
(ultrafiltration rate and volume, plasma
osmolality reduction) and
patient-relat-ed factors (hypovolemia, cardiac
dys-function, vasodilation).
9,10Intradialytic
hypotension reduces the dialysis dose and
maintains the ischemic lesion, thus
delay-ing AKI recovery.
11When compared with intermittent
treatment, continuous methods provide
for better hemodynamic stability, being
preferable in hemodynamically unstable
patients.
12However, the need for
continu-ing anticoagulation, skilled nurscontinu-ing and
its high cost makes them unavailable in
many centers.
13In this context, since the 1990’s there
have been descriptions of adaptations of
conventional hemodialysis machines for
“semicontinuous” use, seeking thereby to
create a treatment mode that could join
the advantages of the intermittent and the
continuous methods.
14,15It all resulted in
intermittent therapies. This modality is now
increas-ingly being used by nephrologists.
16E
XTENDED HEMODYALISIS(EH) -
PHYSIOLOGICAL ANDTECHNICAL ASPECTSThe physiological basis of EH is a longer duration
procedure (with a decreased ultrafiltration/hour rate),
with reduced dialysate and blood flow, thus
minimi-zing osmotic imbalance, but without decreasing solute
clearance.
17The hemodynamic stability is comparable
to that of continuous procedures, as well as the dialysis
dose supplied, which is equivalent or even higher than
continuous and intermittent treatment modalities.
18EH uses the same machines as conventional
he-modialysis, usually adapted to provide reduced blood
(100-200 ml/min) and dialysate (100-300 ml/min)
flow. The session duration is increased to 6 to 18 hours
(mean of 8 hours)
19and in some situations there is
also the possibility for continuous mode operation.
20The session duration, as well as the goals of
ultrafil-tration, vary according to the degree of hemodynamic
instability. Furthermore, the use of low-temperature
dialysate (35 degrees), higher levels of calcium in the
dialysate (3.5 mEq/l) and sodium and ultrafiltration
profiles are often associated to minimize the risk of
hypotension (Table 1).
21,22as in patients with decompensated heart and liver
dis-eases - patients more prone to intradialytic hypotension.
Another EH advantage is the possibility of having
evening sessions, not limited to diagnostic procedures
during daytime.
19Since it uses the same equipment
used in conventional intermittent hemodialysis, the
costs get to be 6-8 times lower than in continuous
treatment.
24C
LINICAL EXPERIENCE INEH
USE IN CRITICALLY-ILL PATIENTS
Several recently published studies confirm the good
hemodynamic tolerability and effective dialysis doses
associated with prolonged hemodialysis, even when
compared to continuous treatments.
In one of the first publications on this topic,
Marshall
et al
.,
26analyzed 37 patients submitted to
EH sessions (12 hours) and reported excellent solute
removal and hemodynamic stability, with less than
8% of sessions suspended for refractory
hypoten-sion. The mortality rate was comparable to that of
continuous treatments.
In extended hemodialysis sessions (8 hours, six
times per week), Berbece
et al
.
24found higher dialysis
doses when compared to continuous hemofiltration.
Kumar
et al
.
13compared patients under daily
treatment with continuous hemodialysis and HE
(mean duration of 7.5 hours per session). There was
no significant difference in mean arterial pressure
during or after the procedure; ultrafiltration goals
were similar between the groups (3.000 ml/day versus
3.028 ml/day). In addition, there was significant
re-duction in the heparin dose used (mean 4.000 IU/day
versus
21.000 IU/day).
Kielstein
et al
.
27analyzed patients undergoing
ex-tended hemodialysis sessions (12 hour-sessions) and
continuous hemofiltration. Again, there was no
varia-tion vis-à-vis blood pressure, need for vasoactive drugs
and cardiac output during the sessions. The urea
re-duction rates of both modalities were similar and urea
indices normalization was faster with EH. In a
simi-lar study (8-hour HE sessions), Fieghen
et al
.
28also
observed no differences in relation to hemodynamic
instability between EH and continuous therapies.
The HANNOVER
29study showed similar survival
(14 and 28 days) and renal function recovery after 1
month in patients treated with standard EH (urea
tar-get 120-150 mg/dl) or intensive EH (urea lower than
T
ABLE1
E
XTENDEDHEMODIALYSISPRESCRIPTIONMODELDuration 6-8 hours
Blood flow 100-200 (ml/min)
Dialysate flow 200-300 (ml/min)
Ultrafiltration Variable (maximum around
250 ml/h) + profile
Sodium Fixed 145-150 mEq/L or
profile
Dialysate temperature 35ºC
Anticoagulation Unfractionated heparin
500-1000 UI/hour
There is no difference regarding dialyzers (high or
low flow) and the dialysate. Anticoagulation can be
done with unfractionated heparin (doses being 50%
to 75% lower than in continuous treatment), citrate
23or saline solution flush.
24disease and encephalopathy, there are reports that
EH was effective in maintaining cerebral blood flow,
avoiding increases in intracranial pressure.
37In cases of exogenous poisoning (salicylate and
lithium), EH also proved effective, with effects
compa-rable to those achieved with continuous therapies.
38,39With the spread of EH in the ICU, recent studies
have evaluated the pharmacokinetic changes caused
on some antibiotics. Thus, drugs such as
vancomy-cin, carbapenems, linezolid and ampicillin-sulbactam
should have their doses increased and supplemented
after EH completion.
40-42C
ONCLUSIONIn Europe and the United States, EH still accounts
for only 25% of ICU dialyses.
43,44In Brazil, especially
because of the lack of continuous treatment in most
centers, EH emerges as an important therapeutic
alternative for critically ill patients, and its use should
be increasingly encouraged.
Recent published studies have proven its efficiency
in terms of supplied dialysis dose, hemodynamic
sta-bility, and in mortality and renal function recovery
rates, very close to or even higher than those achieved
with continuous treatment. Even the addition of
con-vective clearance - which before was an exclusive
op-tion of continuous procedures, it is now held in
pro-longed intermittent treatment with lower costs. For
these reasons, EH is becoming the dialysis method
in-creasingly used in hemodynamically unstable patients
in the ICU.
45,46R
EFERENCES1. Ricci Z, Ronco C. Dose and efficiency of renal replacement therapy: continuous renal replacement therapy versus in-termittent hemodialysis versus slow extended daily dialysis. Crit Care Med 2008;36:S229-37. http://dx.doi.org/10.1097/ CCM.0b013e318168e467 PMid:18382199
2. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Mor-gera S, et al.; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005;294:813-8. http://dx.doi.org/10.1001/jama.294.7.813 PMid:16106006
3. Ricci Z, Ronco C, D'Amico G, De Felice R, Rossi S, Bolgan I, et al. Practice patterns in the management of acute renal failu-re in the critically ill patient: an international survey. Nephrol Dial Transplant 2006;21:690-6. http://dx.doi.org/10.1093/ndt/ gfi296 PMid:16326743
4. Davenport A. Renal replacement therapy in acute kidney in-jury: which method to use in the intensive care unit? Saudi J Kidney Dis Transpl 2008;19:529-36. PMid:18580008 5. Gabriel DP, Caramori JT, Martin LC, Barretti P, Balbi AL.
Con-tinuous peritoneal dialysis compared with daily hemodialysis in patients with acute kidney injury. Perit Dial Int 2009;29 Suppl
90 mg/dl). Palevsky
et al
.
30showed that EH - either
intensive (mean of 5.4 sessions/week) or
convention-al (mean of 3 sessions/week) showed no differences
in mortality and kidney survival when compared
to continuous treatment (similar dialysis dose and
ultrafiltration targets).
In a multicentric and randomized study, Marshall
et al
.
31showed that the conversion of continuous
hemodialysis into EH (EH either extended or
conven-tional hemodiafiltration) did not affect the mortality
of patients while maintaining good hemodynamic
tol-erability and kidney function recovery.
In a recent publication, Schwenger
et al
.
32compared
extended hemodialysis (115 patients, 817 sessions)
and continuous hemodialysis (117 patients, 877
ses-sions) in a prospective randomized study. After 90
days, mortality in both groups was the same. There
was no difference in hemodynamic stability. EH
pa-tients spent less time on mechanical ventilation and
fewer days in the ICU, and had lower demand for
nursing care during dialysis, thereby generating lower
costs.
O
THERCLINICALASPECTSANDRELEVANTAPPLICATIONSContinuous approaches enable the association of
convective and diffusive clearance (continuous
he-mofiltration and hemodiafiltration). Similarly, EH
may also be broadened to perform extended
hemo-diafiltration. In this technique, there is an increased
elimination of medium-size molecules and
inflamma-tory mediators as well as the dialysis dose supplied.
Marshall
et al
.
33analyzed 56 extended
hemodiafil-tration sessions (8 hours) in 24 patients, and found
no complications associated with hypotension (such
as the introduction of new inotropic agents). The
dialysis dose of was high and costs are lower when
compared to continuous hemodiafiltration, due to the
online generation of replacement fluids.
34Abe
et al
.
35observed that extended
hemodiafiltra-tion (6-8 hours, minimum replacement volume of 14
liters) showed higher doses of dialysis and renal
re-covery rates when compared to continuous
hemodi-afiltration, and shorter hospital stay.
In severe cardiac functional class IV patients, with
hemodynamic instability, resistant to diuretics and
techniques of conventional hemodialysis, clinical
im-provement was evident with EH.
366. Vanholder R, Van Biesen W, Lameire N. What is the renal re-placement method of first choice for intensive care patients? J Am Soc Nephrol 2001;12 Suppl 17:S40-3. PMid:11251030 7. Uehlinger DE, Jakob SM, Ferrari P, Eichelberger M, Huynh-Do
U, Marti HP, et al. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 2005;20:1630-7. http://dx.doi.org/10.1093/ndt/ gfh880 PMid:15886217
8. Vinsonneau C, Camus C, Combes A, Costa de Beauregard MA, Klouche K, Boulain T, et al. Continuous venovenous haemo-diafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet 2006;368:379-85. http:// dx.doi.org/10.1016/S0140-6736(06)69111-3
9. Doshi M, Murray PT. Approach to intradialytic hypotension in intensive care unit patients with acute renal failure. Artif Organs 2003;27:772-80. http://dx.doi.org/10.1046/j.1525-1594.2003.07291.x PMid:12940898
10. Murray P, Hall J. Renal replacement therapy for acute renal failure. Am J Respir Crit Care Med 2000;162:777-81. http:// dx.doi.org/10.1164/ajrccm.162.3.ncc400 PMid:10988080 11. Garg N, Fissell WH. Intradialytic hypotension: a case for
going slow and looking carefully. Nephrol Dial Trans-plant 2013;28:247-9. http://dx.doi.org/10.1093/ndt/gfs316 PMid:22848109
12. Uchino S, Ronco C. Continous Renal Replacement Theraphy. In: Jorres A, Ronco C, Kellum JA, editors. Management of Acu-te Kidney Problems. 1st ed. New York: Springer; 2010. p.525-35. http://dx.doi.org/10.1007/978-3-540-69441-0_52 13. Kumar VA, Craig M, Depner TA, Yeun JY. Extended
dai-ly diadai-lysis: A new approach to renal replacement for acu-te renal failure in the inacu-tensive care unit. Am J Kidney Dis 2000;36:294-300. http://dx.doi.org/10.1053/ajkd.2000.8973 PMid:10922307
14. Kihara M, Ikeda Y, Shibata K, Masumori S, Fujita H, Ebira H, et al. Slow hemodialysis performed during the day in managing renal failure in critically ill patients. Nephron 1994;67:36-41. http://dx.doi.org/10.1159/000187885 PMid:8052365
15. Marshall MR, Golper TA, Shaver MJ, Alam MG, Chatoth DK. Urea kinetics during sustained low-efficiency dialysis in critically ill patients requiring renal replacement therapy. Am J Kidney Dis 2002;39:556-70. http://dx.doi.org/10.1053/ajkd.2002.31406 PMid:11877575
16. Fliser D, Kielstein JT. Technology Insight: treatment of renal failure in the intensive care unit with extended dialysis. Nat Clin Pract Nephrol 2006;2:32-9. http://dx.doi.org/10.1038/ ncpneph0060 PMid:16932387
17. Marshall MR, Golper TA. Low-efficiency acute renal replacement therapy: role in acute kidney injury. Semin Dial 2011;24:142-8. http://dx.doi.org/10.1111/j.1525-139X.2011.00829.x PMid:21517979
18. Marshall M, Shaver M, Alam M, Chatoth D. Prescribed versus delivered dose of sustained low-efficiency dialysis (SLED) [Abs-tract]. J Am Soc Nephrol 2000;11:324A.
19. Lima EQ, Burdmann EA, Yu L. Adequação de diálise em insu-ficiência renal aguda. J Bras Nefrol 2003;25:149-54.
20. Salahudeen AK, Kumar V, Madan N, Xiao L, Lahoti A, Samuels J, et al. Sustained low efficiency dialysis in the con-tinuous mode (C-SLED): dialysis efficacy, clinical outcomes, and survival predictors in critically ill cancer patients. Clin J Am Soc Nephrol 2009;4:1338-46. http://dx.doi.org/10.2215/ CJN.02130309 PMid:19628685 PMCid:2723965
21. Paganini EP, Sandy D, Moreno L, Kozlowski L, Sakai K. The effect of sodium and ultrafiltration modelling on plasma vo-lume changes and haemodynamic stability in intensive care patients receiving haemodialysis for acute renal failure: a pros-pective, stratified, randomized, cross-over study. Nephrol Dial Transplant 1996;11 Suppl 8:32-7. http://dx.doi.org/10.1093/ ndt/11.supp8.32 PMid:9044338
22. Lima EQ, Silva RG, Donadi EL, Fernandes AB, Zanon JR, Pinto KR, et al. Prevention of intradialytic hypotension in pa-tients with acute kidney injury submitted to sustained low-effi-ciency dialysis. Ren Fail 2012;34:1238-43. http://dx.doi.org/10 .3109/0886022X.2012.723581 PMid:23006063
23. Clark JA, Schulman G, Golper TA. Safety and efficacy of re-gional citrate anticoagulation during 8-hour sustained low-effi-ciency dialysis. Clin J Am Soc Nephrol 2008;3:736-42. http:// dx.doi.org/10.2215/CJN.03460807 PMid:18272829 PM-Cid:2386695
24. Berbece AN, Richardson RM. Sustained low-efficiency dialysis in the ICU: cost, anticoagulation, and solute removal. Kidney Int 2006;70:963-8. http://dx.doi.org/10.1038/sj.ki.5001700 PMid:16850023
25. Costa MC, Curvello Neto AL, Yu L. Métodos hemodiáliticos contínuos para tratamento da Insuficiência Renal Aguda. In Rie-lla MC. Princípios de Nefrologia e Distúrbios Hidroeletrolíticos. 5ª ed. Rio de Janeiro: Guanabara-Koogan; 2010. p.1020-31. 26. Marshall MR, Golper TA, Shaver MJ, Alam MG, Chatoth
DK. Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy. Kidney Int 2001;60:777-85. http://dx.doi.org/10.1046/j.1523-1755.2001.060002777.x PMid:11473662
27. Kielstein JT, Kretschmer U, Ernst T, Hafer C, Bahr MJ, Haller H, et al. Efficacy and cardiovascular tolerability of extended dialysis in critically ill patients: a randomized con-trolled study. Am J Kidney Dis 2004;43:342-9. http://dx.doi. org/10.1053/j.ajkd.2003.10.021 PMid:14750100
28. Fieghen HE, Friedrich JO, Burns KE, Nisenbaum R,
Adhikari NK, Hladunewich MA, et al.; University of Toronto Acute Kidney Injury Research Group. The hemodynamic tole-rability and feasibility of sustained low efficiency dialysis in the management of critically ill patients with acute kidney injury. BMC Nephrol 2010;25;11-32.
29. Faulhaber-Walter R, Hafer C, Jahr N, Vahlbruch J, Hoy L, Haller H, et al. The Hannover Dialysis Outcome study: compa-rison of standard versus intensified extended dialysis for treat-ment of patients with acute kidney injury in the intensive care unit. Nephrol Dial Transplant 2009;24:2179-86. http://dx.doi. org/10.1093/ndt/gfp035 PMid:19218540
30. VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Chou-dhury D, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359:7-20. http:// dx.doi.org/10.1056/NEJMoa0802639 PMid:18492867 PM-Cid:2574780
31. Marshall MR, Creamer JM, Foster M, Ma TM, Mann SL, Fiac-cadori E, et al. Mortality rate comparison after switching from continuous to prolonged intermittent renal replacement for acute kidney injury in three intensive care units from different countries. Nephrol Dial Transplant 2011;26:2169-75. http:// dx.doi.org/10.1093/ndt/gfq694 PMid:21075821
32. Schwenger V, Weigand MA, Hoffmann O, Dikow R, Kihm LP, Seckinger J, et al. Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury - a randomi-zed interventional trial: the REnal Replacement Therapy Stu-dy in Intensive Care Unit PatiEnts. Crit Care 2012;16:R140. http://dx.doi.org/10.1186/cc11815 http://dx.doi.org/10.1186/ cc11445 PMid:22839577 PMCid:3580725
33. Marshall MR, Ma T, Galler D, Rankin AP, Williams AB. Sus-tained low-efficiency daily diafiltration (SLEDD-f) for critically ill patients requiring renal replacement therapy: towards an adequate therapy. Nephrol Dial Transplant 2004;19:877-84. http://dx.doi.org/10.1093/ndt/gfg625 PMid:15031344 34. Holt BG, White JJ, Kuthiala A, Fall P, Szerlip HM. Sustained
35. Abe M, Okada K, Suzuki M, Nagura C, Ishihara Y, Fujii Y, et al. Comparison of sustained hemodiafiltration with continuous venovenous hemodiafiltration for the treatment of critically ill patients with acute kidney injury. Artif Organs 2010;34:331-8. http://dx.doi.org/10.1111/j.1525-1594.2009.00861.x PMid:20420616
36. Violi F, Nacca RG, Iengo G, Iorio L, et al. Long-term sustained low efficiency dialysis in eight patients with class IV NYHA heart failure resistant to high-dose diuretic treatment. G Ital Nefrol 2009;26 Suppl 46:50-2. PMid:19644818
37. Bandyopadhyay S, Jakobson D, Chhabra KD, Baker A . Im-provement of cerebral blood flow patterns in hepatorenal syndrome using sustained low-efficiency dialysis. Br J Anaes-th 2010;105:547-8. http://dx.doi.org/10.1093/bja/aeq253 PMid:20837726
38. Fiaccadori E, Maggiore U, Parenti E, Greco P, Cabassi A. Sus-tained low-efficiency dialysis (SLED) for acute litium intoxica-tion. Clin Kidney J 2008;1:329-32.
39. Lund B, Seifert SA, Mayersohn M. Efficacy of sustained low-efficiency dialysis in the treatment of salicylate toxici-ty. Nephrol Dial Transplant 2005;20:1483-4. http://dx.doi. org/10.1093/ndt/gfh796 PMid:15797887
40. Bogard KN, Peterson NT, Plumb TJ, Erwin MW, Fuller PD, Olsen KM. Antibiotic dosing during sustained low-efficiency dialysis: special considerations in adult critically ill patients. Crit Care Med 2011;39:560-70. http://dx.doi.org/10.1097/ CCM.0b013e318206c3b2 PMid:21221000
41. Mushatt DM, Mihm LB, Dreisbach AW, Simon EE. An-tibiotic dosing in slow extended daily dialysis. Clin In-fect Dis 2009;49:433-7. http://dx.doi.org/10.1086/600390 PMid:19580416
42. Lorenzen JM, Broll M, Kaever V, Burhenne H, Hafer C, Clajus C, et al. Pharmacokinetics of ampicillin/sulbactam in cri-tically ill patients with acute kidney injury undergoing extended dialysis. Clin J Am Soc Nephrol 2012;7:385-90. http://dx.doi. org/10.2215/CJN.05690611 PMid:22223613 PMCid:3302675 43. Ricci Z, Ronco C, D'Amico G, De Felice R, Rossi S, Bolgan I,
et al. Practice patterns in the management of acute renal failu-re in the critically ill patient: an international survey. Nephrol Dial Transplant 2006;21:690-6. http://dx.doi.org/10.1093/ndt/ gfi296 PMid:16326743
44. Overberger P, Pesacreta M, Palevsky PM.; VA/NIH Acute Re-nal Failure Trial Network. Management of reRe-nal replacement therapy in acute kidney injury: a survey of practitioner prescri-bing practices. Clin J Am Soc Nephrol 2007;2:623-30. http:// dx.doi.org/10.2215/CJN.00780207 PMid:17699474 PM-Cid:2325917
45. Vanholder R, Van Biesen W, Hoste E, Lameire N. Pro/con debate: continuous versus intermittent dialysis for acute kid-ney injury: a never-ending story yet approaching the finish? Crit Care 2011;15:204. http://dx.doi.org/10.1186/cc9345 PMid:21345275 PMCid:3222013
